Stereoselective construction of the pyrrolizidine bridgehead stereochemistry by the adjacent hydroxyl group in the synthesis of (+)-heliotridine and (−)-retronecine

Formal total synthesis of (+)-heliotridine (4) and total synthesis of (−)-retronecine (5) were accomplished by using (S)-3-acetoxysuccinimide (6) as the common starting material. The stereogenic center of 6 ended up as C-1 in both alkaloids. The chiral centers at C-7a of the alkaloids were stereoselectively constructed through the help of the adjacent functionality at C-1. The B-rings of the alkaloids were formed through α-sulfonyl radical cyclizations.     

Structures of new alkaloids sessilifoliamides A-D from Stemona sessilifolia

Four new Stemona alkaloids, sessilifoliamides A-D (1-4), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine (5), 2-oxostenine (6), stemoninoamide (7), tuberostemonone (8), and neotuberostemonol (9). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, ¹H, ¹³C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Mosher's method.     

Four novel gelsedine-type oxindole alkaloids from Gelsemium elegans

Four new gelsedine-type oxindole alkaloids (1-4) were isolated from the leaves and branches of Gelsemium elegans, together with 10 known alkaloids. The structures of the new alkaloids were determined by spectroscopic analyses and partial synthesis from known compounds. Gelsecrotonidine (1), 14-hydroxygelsecrotonidine (2), and 11-methoxygelsecrotonidine (3) possess an additional C₂ unit with an acetic acid residue compared to gelsenicine-related monoterpenoid indole alkaloids. 14-Hydroxygelsedilam (4) is an 18,19-nor-type monoterpenoid indole alkaloid.     

A divergent approach for the total syntheses of cernuane-type and quinolizidine-type Lycopodium alkaloids

The divergent total syntheses of cernuane-type and quinolizidine-type Lycopodium alkaloids are described. A common intermediate 5 for the two types of alkaloids was assembled practically from (+)-citronellal via organocatalytic α-amination, followed by the construction of oxazolidinone that was used for diastereoselective allylation. Key compound 5 was converted into cermizine C (3), and this in turn was converted into senepodine G (4) by the regioselective Polonovsky-Potier reaction. The total synthesis of representative cernuane-type alkaloids, (−)-cernuine (1) as well as (+)-cermizine D (2), was also accomplished from 5 by utilizing asymmetric transfer aminoallylation as a key step.     

Positional isomerization of quinine and quinidine via rhodium on alumina catalysis: practical one-step synthesis of Δ-isoquinine and Δ-isoquinidine

The synthesis of Δ^3,10-isoquinine (5Z,5E) and Δ^3,10-isoquinidine (6Z,6E) was achieved in one-step through positional isomerization of the terminal alkene in the parent cinchona alkaloids using catalytic amounts of 5% Rh/Al₂O₃ and excess hydrochloric acid in refluxing 50% aqueous EtOH. The products were obtained in good yields as a mixture of E and Z geometric isomers and fully characterized using spectroscopic methods.     

Total synthesis of suaveoline and norsuaveoline via intramolecular oxazole-olefin Diels-Alder reaction

Total synthesis of two Rauwolfia alkaloids, suaveoline (1) and norsuaveoline (2), has been achieved through a highly stereoselective route starting from l-tryptophan methyl ester (9) and exploiting the intramolecular Diels-Alder reaction of the oxazole-olefin 16.     

Isolation and total syntheses of two new alkaloids, dubiusamines-A, and -B, from Pandanus dubius

Chemical investigation of the crude base of Pandanus dubius led to the isolation of two new alkaloids, dubiusamine-A (1) and dubiusamine-B (2). The structures of the two alkaloids including their absolute configuration were unambiguously confirmed by 1D and 2D NMR analysis and asymmetric total synthesis.     

Facile conversion of 2-azetidinones to 2-piperidones: application to a formal synthesis of Prosopis and Cassia alkaloids

Nonracemic 5,6-disubstituted 2-piperidones were prepared from readily accessible 3,4-disubstituted-2-azetidinones having pre-installed substituents by reductive ring opening of 2-azetidinones followed by stereoselective installation of Z-α,β-unsaturated ester and lactam formation. For the synthetic application to the naturally occurring piperidine alkaloids, such as Prosopis and Cassia alkaloids, 5-hydroxy-2-piperidones (+)-13 and (−)-24 were prepared from 2-azetidinones (−)-6b and (+)-18 via two-carbon ring homologation.     

New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C₁₆N₂ type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1-4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7-10.     

Total synthesis of the naphthyridine alkaloid jasminine

The synthesis of (±)-jasminine (1), a member of a small group of naphthyridine alkaloids, has been achieved. The synthetic route takes advantage of the reactivity of dihydropyridine intermediates for the preparation of trisubstituted pyridine 4, which gives access to the alkaloid by a reductive amination-lactamization tandem reaction.     

Total synthesis of aspergillide B and structural discrepancy of aspergillide A

Fourteen-membered cytotoxic macrolides 1 and 2 were synthesized from alcohol 10 in 15 steps utilizing stereospecific Pd(II)-catalyzed cyclization of ζ-hydroxy chiral allylic alcohol 7. Aspergillides A and B were isolated from marine fungus, and their structures were proposed as 1 and 2, respectively. The synthetic 1 was not matched with aspergillide A but matched with aspergillide B. The chiral center at C-13 position of aspergillide B was revised to be (S)-configuration. The key steps of the stereoselective synthesis include the Sharpless asymmetric dihydroxylation, cross-metathesis, stereospecific construction of tetrahydropyran ring of 16 using Pd^II catalyst, and the Yamaguchi macrolactonization.     

Isolation,characterization, and NMR spectroscopic data of indole and oxindole alkaloids from Mitragyna speciosa

A new indole alkaloid, 7β-hydroxy-7H-mitraciliatine (1) and a new oxindole alkaloid, isospeciofoleine (2) together with nine known alkaloids were isolated from Mitragyna speciosa and characterized by NMR, CD, and MS spectroscopic data analyses. The ¹H and ¹³C NMR spectroscopic data of isospeciofoline (3), isorotundifoline (4), paynantheine (5), and 3-isopaynantheine (6) were also reported for the first time.     

Total synthesis of (±)-luminacin D

A 15-step synthesis of (±)-luminacin D from ethyl pent-2-ynoate is reported. The pivotal step involves the formation of the central C-2′/C-3′ bond of the natural product by condensation of the titanium enolate derived from aromatic ketone 1 with aldehyde 2a. A remote asymmetric centre in aldehyde 2a exerts control over the stereochemical course of this reaction, with the major adduct (3a, 54% yield) possessing the required (2′S^∗,3′R^∗,5′R^∗)-stereochemistry. This assignment was unambiguously established by X-ray crystallography of late stage synthetic intermediate, 17. Further manipulation of 3a (six steps) yielded synthetic (±)-luminacin D spectroscopically identical to material isolated from Streptomyces sp. Mer-VD1207 by Naruse et al.     

Caldaphnidines A-F, six new Daphniphyllum alkaloids from Daphniphyllum calycinum

Six new Daphniphyllum alkaloids, namely caldaphnidines A-F (1-6), together with eight known ones, deoxycalyciphylline B, deoxyisocalyciphylline B, bukittiggine, calycicine A, methyl homosecodaphniphyllate, daphnilactone B, and daphnezomines L-M, were isolated from the leaves and the seeds of Daphniphyllum calycinum. The structure of 1 was determined by a single-crystal X-ray diffraction study, and the structures of 2-6 were established by spectral methods, especially two-dimensional NMR techniques (¹H-¹H COSY, HMQC, HMBC, and NOESY).     

Studies directed towards the stereoselective total synthesis of ilexlactone via a tandem ring-closing enyne metathesis protocol

Studies directed towards the stereoselective total synthesis of ilexlactone resulted in the synthesis of bicyclic systems 1a, 1b and ent-1a through tandem ring-closing enyne metathesis using Grubbs’ catalyst. The structures of synthetic 1a, 1b and ent-1a revealed that the proposed structure for ilexlactone is incorrect.     

Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.

Chemical fractionation of the southern Australian marine sponge Phoriospongia sp. (CMB-03107) yielded phorioadenine A (1) as a nematocidal agent and the first reported example of a 6-N-acyladenine natural product. The structure of 1 was confirmed by spectroscopic analysis and the chemical synthesis of racemic (1a) and enantiomeric (1b) analogues. HPLC–ESIMS analysis of the crude sponge extract with comparisons to the synthetic 6-N-acyladenosine 2a provided evidence that the biosynthetically related adenosine, phorioadenosine A (2), was present as a trace co-metabolite. The rare starfish metabolite asterubine (3) was also isolated as a co-metabolite, and its structure confirmed by spectroscopic analysis and chemical synthesis. Biological investigations confirmed that natural products 1–3 and synthetic analogues 1a–e and 2a were not cytotoxic to multiple mammalian cancer cell lines, or Gram-positive or -negative bacteria. Nematocidal activity (inhibition of larval development of Haemonchus contortus) detected in the Phoriospongia sp. extract was attributed to 1 (LD₉₉ 31 μg/mL), with preliminary structure–activity relationship investigations confirming the importance of the N-acyl side chain.     

Polyketide origin of 3-alkylpyridines in the marine mollusc Haminoea orbignyana

The paper reports the biosynthesis of the main alkylpyridine alkaloids, haminol-1 (1) and -2 (2), in the Mediterranean mollusc Haminoea orbignyana. Experiments were carried out by in vivo incorporation of [1,2- ¹³C₂ acetate]. Data give full account for a polyketide origin of haminols in the Mediterranean molluscs, showing the biosynthesis of these 3-alkylpyridine alkaloids by elongation with acetate of a starter unit of nicotinic acid.     

Three new monoterpene indole alkaloids from Psychotria umbellata Thonn.

Three new psychollatine-derived monoterpene indole alkaloids were obtained from Psychotria umbellata Thonn.: 3,4-Dehydro-18,19-β-epoxy-psychollatine (2), N⁴-[1-((R)-2-hydroxypropyl)]-psychollatine (3), and N⁴-[1-((S)-2-hydroxypropyl)]-psychollatine (4). Their structures were determined by ¹H and ¹³C NMR spectra, 2D correlations (COSY, HMQC, and HMBC), and mass and UV spectra. Compounds 3 and 4 were synthesized for structural confirmation and for the determination of the stereochemistry of the hydroxyl group.     

A concise approach to (+)-1-epi-castanospermine

A concise enantioselective synthesis of (+)-1-epi-castanospermine (2) is described, which featured the use of chiral non-racemic tetramic acid derivative 5 as a synthetic equivalent of the challenging synthon A through a highly diastereoselective vinylogous Mukaiyama type reaction.     

New synthetic technology for the construction of N-hydroxyindoles and synthesis of nocathiacin I model systems

A new synthetic method providing expedient access to a wide range of polyfunctionalized N-hydroxyindoles (IV) is reported. These unique constructs are assembled by nucleophilic additions to in situ generated α,β-unsaturated nitrones (III) through carbon-carbon and carbon-heteroatom bond formation. The new synthetic technology was applied to the synthesis of nocathiacin I (1) model systems (2 and 3a-c) containing the N-hydroxyindole structural motif.